Gaucher's disease is a lysosomal, sphingolipidosis characterized by the accumulation of glucocerebroside in the cells of the reticuloendothelial system. The disease occurs most frequently in adults and involves primarily splenomegaly and bone disease; the central nervous system in rarely involved. The disease presents only rarely in infants and juveniles with devastating pathology of the central nervous system. The molecular basis that distinguishes the two forms of Gucher's disease is unknown. Our primary objective is to define this biochemical distinction. We will purify and characterize the membrane-bound glucocerebrosidase of human brain and liver. The distinct cytoplasmic aryl beta glucosidase of human liver will also be isolated and characterized. The beta-xylosidase that we have found to be totally absent from the brains of three neurologic cases of Gaucher's disease will be purified to homogeneity and characterized. Finally, the structure of the heat-stable activator of glucocerebrosidase from Gaucher spleen will be determined. In addition, the mechanism of action of the heat-stable factor will be investigated.